Process for making 2-aryl benz (ox, thi, imid)azoles and 2-aminoaryl aminobenz(ox, thi, imid)azoles

ABSTRACT

2-(aryl)-benz(ox, thi, imid)azoles are prepared by reacting an aromatic aldehyde with hydroxylamine to form an aromatic aldehyde oxime, halogenating the oxime to form an aromatic hydroxamoyl halide, and then reacting this halide with certain aromatic amine compounds. The products may be nitrated and then reduced to form the corresponding diamines, which are useful in making PIBX polymers.

BACKGROUND OF THE INVENTION

This invention relates to a process for making 2-aryl benz(ox, thi,imid)azoles and 2-aminoaryl amino-benz(ox, thi, imid)azoles. The term"benz(ox, thi, imid)azole" is used herein as a shorthand term todesignate an oxazole, thiazole or imidazole group which is fused to anaromatic ring at the 4 and 5 positions.

Polyimide benz(ox, thi, imid)azole (PIBX) polymers can be prepared byreacting a dianhydride with a diamine containing one or more benz(ox,thi, imid)-azole groups. See, for example U.S. Pat. No. 4,087,409 toPreston, incorporated herein by reference. Among the useful benz(ox,thi, imid)azole-containing diamines are those in which the 2 position ofthe oxazole ring is substituted with an aminoaryl group. Among thediamines of the latter type are those represented by the structure:##STR1## wherein X is --O--, --S--, or --NH--.

These latter amines can be prepared by reacting an amino benzoic acidwith 2,4- or 2,5-diamino phenol, 2,4- or 2,5-diamino phenyl mercaptan,or 1,2,4- triaminobenzene (when X is --O--, --S--, and --NH--,respectively). For example, it is known to prepare2-(m-aminophenyl)-aminobenzoxazole (DAMBO) by reacting 2,4-diaminophenolwith meta- or para-aminobenzoic acid in the presence of polyphosphoricacid. Unfortunately, however, this process suffers from severaldrawbacks. The reaction mixture requires extensive neutralization, andthus forms large volumes of aqueous phosphate salts as a waste stream.The product must be purified extensively through repeated sublimationsin order to be useful as a monomer. In addition, the diaminophenol andaminobenzoic acid starting materials are expensive and not readilyavailable.

For these reasons, it would be desirable to provide an alternate methodfor making DAMBO as well as other 2-aminoaryl aminobenz(ox, thi,imid)azoles.

SUMMARY OF THE INVENTION

In one aspect, this invention is a process for preparing a2-(aryl)-benz(ox, thi, imid)azole, comprising:

(a) contacting an aromatic aldehyde with hydroxylamine under conditionssuch that an aromatic aldehyde oxime is formed;

(b) contacting said aromatic aldehyde oxime with a halogenating agentunder conditions such that an aromatic hydroxamoyl halide is formed; and

(c) contacting the aromatic hydroxamoyl halide with an aromatic aminecompound which has a primary amine group ortho to a hydroxyl group, athiol group or another primary amine group to form a 2-(aryl)-benz(ox,thi, imid)azole.

In this process, both the aromatic aidehyde and the aromatic aminecompound may be nitro-substituted. In such case, the nitro group orgroups may be reduced to primary amine groups after step (c). In thecase where neither, or only one of the aromatic aldehyde and thearomatic amine compound is nitro-substituted, the benz(ox, thi,imid)azole may be nitrated after step (c) so that following thenitration, both the benz(ox, thi, imid)azole and the aromaticsubstituent at the 2-position contain a nitro group. These nitro groupsmay be then reduced to amines.

Steps (a), (b), and (c) can be performed under mild conditions to obtainhigh yields of benz(ox, thi, imid)azole at essentially 100% selectivity,and do not require the use of polyphosphoric acid. Moreover, the processof this invention makes use of relatively inexpensive startingmaterials.

DETAILED DESCRIPTION OF THE INVENTION

In the first step of this process, an aromatic aldehyde is contactedwith hydroxylamine under conditions such that an aromatic aldehyde oximeis formed. By "aromatic aldehyde", it is meant a compound in which agroup represented by the structure:

    --CH═N--OH

is bonded directly to an aromatic nucleus of an aromatic ring structure.

The aromatic aldehyde is a compound having a --CHO group directly bondedto an aromatic nucleus of an aromatic ring structure. Suitable aromaticring structures to which the --CHO group is bonded include pyridine,benzene and fused ring systems such as anthracene, naphthalene and thelike. The aromatic ring structure may be unsubstituted or substituted.However, any substituted ring structure must contain either a hydrogenor a nitro group attached to an aromatic nucleus, or else at least oneof the substituent groups must be capable of being replaced by a nitrogroup after the benz(ox, thi, imid)azole is formed. In addition, anysubstituent group should not react under the conditions of the reactionwith hydroxylamine with the aromatic aidehyde, or of the subsequentreactions with a halogenating agent and with the aromatic aminecompound. Suitable substituents include phenyl, phenoxyl, --SO₂ --(C₆H₅) and the like. It is preferred, but not necessary, that the aromaticaldehyde contain a nitro group bonded to an aromatic ring. Benzaldehydeand mononitrobenzaldehyde are preferred aromatic aldehydes, with m- andp-nitrobenzaldehyde being especially preferred.

The hydroxylamine (H₂ NOH) may be and preferably is used in the form ofa salt of a protic acid, such as the HCl salt. The hydroxylamine ispreferably used in a slight excess relative to the aromatic aldehyde.

The aromatic aldehyde and the hydroxylamine are advantageously contactedin the presence of a solvent or diluent. Preferred solvents are polarmaterials in which both the aldehyde and the hydroxylamine are soluble.Alternatively, nonsolvents can be used as diluents. It is also preferredthat the solvent be one which boils within the preferred or morepreferred temperature range described below, so the reaction may beconducted under refluxing conditions. Suitable solvents include, forexample, ethanol, methanol, isopropanol, 1,4-dioxane, tetrahydrofuran,and polar aprotic solvents that are inert to the reactants and theproducts, as well as toluene and benzene.

The reaction is preferably conducted at an elevated temperature at whichthe aromatic aldehyde does not degrade. A preferred temperature is fromabout 30° to about 120° C., with a temperature from about 50° to about95° C. being more preferred. At the more preferred temperature, areaction time of from about 1/2hour to about 8 hours is generallysufficient to essentially complete the reaction.

The resulting aromatic aldehyde oxime is then reacted with ahalogenating agent under oxidizing conditions to form the correspondingaromatic hydroxamoyl halide. By "aromatic hydroxamoyl halide", it ismeant a compound in which a group represented by the structure:

    --CA═N--OH

is bonded directly to a nucleus of an aromatic ring structure. In theforegoing structure, A represents a halogen atom, preferably chlorine orbromine.

The halogenation proceeds well even under mild conditions, and for thatreason it is preferable to use mild halogenating agents and conditionsin order to avoid halogenation at other sites on the aromatic aldehydeoxime molecule. Suitable halogenating agents include chlorine (Cl₂),bromine (Br₂), hypochlorous acid (HOCl), hypobromous acid, and materialswhich generate hypochlorous or hypobromous acid in situ. Chlorine,bromine, hypochlorous acid and hypobromous acid are advantageously usedas dilute solutions, preferably as aqueous solutions. Materials whichproduce hypochlorous acid in situ include, for example, aqueous mixturesof sodium hypochlorite and a mineral acid, especially HCl; mixtures of aperoxysulfate salt such as potassium peroxysulfate with HCl; andmixtures of N-chlorosuccinamide with aqueous HCl. In analogous fashion,hypobromous acid may be formed in situ from aqueous mixtures of sodiumhypobromite and a mineral acid, mixtures of a peroxysulfate salt such aspotassium peroxysulfate with HBr; and a mixture of N-bromosuccinamidewith aqueous HCl. In preferred embodiments, the halogenating agent is amixture of bleach (sodium hypochlorite solution) with a mineral acid,especially HCl, or an aqueous mixture of a peroxysulfate salt with HClor HBr. In any of these preferred embodiments, HCl or HBr may be used inthe form of an HCl or HBr salt of N,N-dimethylformamide.

The halogenating agent is advantageously used in at least astoichiometric amount, and preferably in slight excess, based on thearomatic aldehyde oxime.

The halogenation reaction may be conducted in the presence of a solventor diluent. The solvents which are useful for the reaction between thearomatic aldehyde and the hydroxylamine are generally useful in thisstep as well.

A suitable temperature for the halogenation step is from about -30° toabout 100° C. preferably from about -10° to about 40° C.

The resulting aromatic hydroxamoyl halide is then reacted with anaromatic amine compound having a primary amine group ortho to a hydroxylgroup, a thiol group, or another primary amino group. In this manner anoxazole, thiazol or imidazole is formed in which an aromatic ringstructure corresponding to that of the aromatic hydroxamoyl halide isbonded to the 2-position. The oxazole, thiazole or imidazole group isformed when the aromatic amine compound contains a hydroxyl, thiol oranother primary amine group, respectively, ortho to a primary aminegroup.

The aromatic amine contains an aromatic ring structure which may bemonocyclic or polycyclic. The aromatic ring structure may containsubstituents other than those mentioned before (i.e., the primary aminegroup and the hydroxyl, thiol or second primary amine group ortho to theprimary amine group). However, any substituted ring structure mustcontain either a hydrogen or a nitro group attached to an aromaticnucleus, or else at least one of the substituent groups must be capableof being replaced by a nitro group after the benz(ox, thi,imid)azole isformed. Further, any substituent group should not react under theconditions of the reaction with the aromatic hydroxamoyl halide to formthe benz(ox, thi, imid)azole. Preferred aromatic amine compounds includethose in which the aromatic ring structure is pyridine, benzene,anthracene, naphthalene, nitropyridine, nitrobenzene, nitroanthracene,nitronaphthalene and the like, of which benzene and nitrobenzene aremore preferred.

The reaction to form the benz(ox, thi, imid)azole can be conducted bymixing the reactants with heating to a temperature from about 20° toabout 150° C. It is advantageous to use a solvent, with those which boilin the stated temperature range being preferred. Among the suitablesolvents are methyl ethyl ketone, 1,4-dioxane, toluene andchlorobenzene. It is preferred to use the aromatic amine compound andthe aromatic hydroxamoyl halide in a mole ratio from about 0.5:1 to1:0.5, more preferably from about 0.7:1 to 1:0.7.

The resulting benz(ox, thi, imid)azole has an aromatic ring structurecorresponding to that of the aromatic amine compound fused to the 4 and5 positions of the benz(ox, thi, imid)azole ring. At the 2 position ofthe benz(ox, thi, imid)azole ring there is another aromatic ringstructure corresponding to that of the aromatic hydroxamoyl halide.

If both of the aromatic ring structures of the benz(ox, thi, imid)azolecontain a nitro group, a 2-aminoaryl-aminobenz (ox, thi, imid)azole isprepared by reducing the nitro groups to amine groups. Any method may beused to accomplish this reduction provided that it selectively reducesthe nitro groups and does not hydrogenate the aromatic rings (includingthe (ox, thi, imid)azole ring). One suitable method is to contact thebenz(ox, thi, imid)azole with hydrogen or other hydrogenating agent inthe presence of a metal catalyst. Suitable metal catalysts includeplatinum and palladium, organometallic complexes of cobalt, nickel,titanium, zirconium and hafnium. The catalyst may be and preferably issupported on a porous support. Platinum and palladium are preferredcatalysts, with platinum on carbon and palladium on carbon beingparticularly preferred. The amount of catalyst is chosen to provide anacceptable reaction rate, and typically is (but is not limited to) fromabout 1 part by weight catalyst per 5 to 5000 parts of the benz(ox, thi,imid)azole to be hydrogenated. It will be understood that many methodsfor conducting this hydrogenation may be used, and the selection of aparticular method is not generally critical to this invention.

In the preferred hydrogenation method, the benz(ox, thi, imid)azole iscontacted with hydrogen at a partial pressure of from about 0 to about5000 psig, at any temperature at which an adequate reaction rate isachieved, preferably from about 25° C. to about 100° C.

When one or both of the aromatic ring structures of the benz(ox, thi,imid)azole lacks a nitro group, it is necessary to nitrate the benz(ox,thi, imid)azole before the reduction is done. The method by which thenitration is accomplished is not critical provided that undesired sidereactions do not occur. Accordingly, the known methods for accomplishingring nitration of aromatic compounds can be used. A preferred method isto contact the benz(ox, thi, imid)azole with nitric acid in the presenceof sulfuric acid, preferably at a temperature range of from about 0° C.to about 25° C. using conditions that prevent multiple nitrations ofeither aromatic ring structure. It is preferred that, following anynitration, each aromatic ring structure contains only one nitro group.Once the needed nitro group or groups are added, they are hydrogenatedto the corresponding primary amine as described before.

The resulting 2-(aminoaryl)-amino benz(ox, thi, imid)azole may berecovered from the reaction mixture by filtering out the catalyst andremoving the solvent.

The 2-(aminoaryl)-amino benz (ox, thi, imid)azole can be used to makePIBX (polyimidebenzoxazole or polyimidebenzthiazole) polymers byreaction with an aromatic dianhydride, as described in the copendingapplication of Hwang et al. entitled POLYAMIC ACIDS AND METHODS TOCONVERT POLYAMIC ACIDS INTO POLYIMIDEBENZOXAZOLE FILMS, Ser. No.331,755, filed Oct. 31, 1994. This reaction is typically conducted intwo stages. In the first stage, the 2-(aminoaryl)-aminobenz(ox, thi,imid)azole and the dianhydride are reacted to form a polyamic acid. Thisis readily accomplished by contacting the dianhydride and the2-(aminoaryl)-aminobenz(ox, thi, imid)azole at a temperature from about-20° C. to about 100° C. in a polar solvent. The resulting polyamic acidmay then be converted to the PIBX by condensing some or all of the amicacid linkages. This is conveniently accomplished by heating the polyamicacid to an elevated temperature which may range up to about 600° C., butis preferably about 160° to about 280° C. Alternatively, a ring-closureagent such as acetic anhydride, proprionic anhydride, ketene orisobutyric dianhydride or salts thereof may be contacted with thepolyamic acid to promote formation of imide rings. Following theimidization reaction, it is preferred to further heat the PIBX to atemperature from about 300° to about 600° C., which improves tensileproperties of the polymer.

The PIBX polymer can be used to make films, fibers or other shapedarticles. Such articles are conveniently prepared by forming a solutionof the PIBO in a suitable solvent and extruding, coating, casting orspraying the solution. Preferably, however, such articles are preparedfrom the polyamic acid solution, which is imidized after the shapedarticle is formed.

The following examples are provided to illustrate the invention, but arenot intended to limit the scope thereof. All parts and percentages areby weight unless otherwise indicated.

EXAMPLE 1

In a 1-liter flask equipped with a reflux condenser and a stirrer ischarged 75 grams (0.5 moles) of 4-nitrobenzaldehyde, 500 milliliters of1,4-dioxane and 38 grams (0.55 moles) of hydroxylamine hydrochloride.The mixture is heated to reflux with stirring for five hours, and thenfiltered. The reaction proceeds essentially quantitatively to form asolution containing approximately 0.5 mole of 4nitrobenzaldoxime.

The resulting 4-nitrobenzaldoxime solution is added to 400 additionalmilliliters of 1,4-dioxane, 100 milliliters of dimethylformamide whichis saturated with 20 grams (0.55 mole) of HCl, and 338 grams (0.55moles) of a potassium peroxysulfate solution sold by DuPont under thetrade designation Oxone. The resulting mixture is stirred for about 18hours, using an ice bath to control the exotherm to below 40° C. Anadditional 5 grams of HCl (dissolved in 50 milliliters ofdimethylformamide) is then added, and the mixture stirred for anadditional 5 hours. The mixture is then washed with acetic acid andwater, and 4-nitrophenylchloroxime (4-nitrophenyl hydroxamoyl chloride)is recovered.

About 60 grams (0.3 mole) of the 4-nitro-phenylchloroxime is mixed with340 milliliters of ethanol, 60 grams (0.39 moles) of2-amino-4-nitrophenol and 60 milliliters of dimethylformamide. Themixture is heated to reflux for about 6.5 hours, filtered, washed withmethanol and air dried. Approximately 55 grams of2-(p-nitrophenyl)-5-nitrobenzoxazole are obtained.

The 2-(p-nitrophenyl)-5-nitrobenzoxazole is dissolved in 500 millilitersof 1,4-dioxane. A 10% palladium-on-carbon catalyst (2.0 grams) is addedand the mixture heated to 70° C. Hydrogen gas is then bubbled into thesolution until liquid chromatography shows that the reduction of thenitro groups is completed. The solvent is then evaporated and theresulting product is recrystallized from ethanol. About 37.5 grams of2-(aminophenyl)-5-aminobenzoxazole is obtained.

EXAMPLE 2

Into 500 milliliters of ethanol are dissolved 75.5 grams (0.5 mole) of4-nitrobenzaldehyde and 38 grams (0.55 mole) of hydroxylaminehydrochloride. The solution is heated at reflux for three hours, thenpoured into water, filtered and dried. Seventy-nine grams of4-nitrobenzaldoxime is recovered.

Twenty-five grams (0.15 moles) of the 4-nitrobenzaldoxime is combinedwith 200 milliliters of 1,4-dioxane and 200 milliliters of concentratedHCl. The mixture is cooled to 10° C. and then 234 grams of a 5.25%aqueous solution of sodium hypochlorite (0.165 moles) are addeddropwise, keeping the temperature of the mixture at about 10° C. Then,200 milliliters of ice water are added, and the resulting mixturefiltered, washed with more ice water, and dried. Twenty-four grams of4-nitrophenylchloroxime (4-nitrophenyl hydroxamoyl chloride) areobtained.

To 10 grams (0.05 mole) of 4-nitrophenylchloroxime are added 150milliliters of ethanol and a catalytic amount of4-(N,N-dimethyl)aminopyridine. 4.0 grams of 2-amino-4-nitrophenol areadded to the mixture. The mixture is stirred under nitrogen at roomtemperature for ninety minutes, at which time another 3.7 grams of1-amino-4-nitrophenol are added. The mixture is then stirred overnightat room temperature under a nitrogen blanket, cooled to 20° C. andfiltered to yield 2-(p-nitrophenyl)-5-nitrobenzoxazole.

A 7.5-gram portion of the 2-(p-nitrophenyl)-5-nitrobenzoxazole isdissolved in 100 milliliters of 1,4-dioxane. A 10% palladium-on-carboncatalyst (2.0 grams) is added, and the mixture stirred under nitrogen.The mixture is heated to 53° C., and hydrogen gas is bubbled into themixture for about 6.5 hours. The catalyst is then filtered off and theremaining solution added to water. The solvent and water are thenevaporated off to yield 2-(p-aminophenyl)-5-aminobenzoxazole.

EXAMPLE 3

Using the general procedure described in Example 2, except that3-nitrobenzaldehyde is used in replace of the 4-benzaldehyde,3-nitrobenzaldoxime is prepared.

A 4.98-gram (0.03 mole) portion of the 3-nitrobenzaldoxime is combinedwith 100 milliliters of 1,4-dioxane and 40 milliliters of concentratedHCl. The mixture is cooled to below 5° C. and then 47 grams of a 5.25%aqueous solution of sodium hypochlorite (0.033 mole) are added dropwise,keeping the temperature of the mixture at about 10° C. Then, 50milliliters of ice water are added, and the resulting mixture isfiltered, washed with more ice water, and dried to produce3-nitrophenylchloroxime ( 3-nitrophenyl hydroxamoyl chloride).

To 11.5 grams (0.05 mole) of 3-nitrophenylchloroxime are added 150milliliters of ethanol. To the mixture are added 23.1 grams (0.15 moles)of 2-amino-4-nitrophenol. The mixture is stirred under nitrogen at about30° C. overnight and filtered to yield2-(m-nitrophenyl)-5-nitrobenzoxazole.

A 11.1-gram portion of the 2-(m-nitrophenyl)-5-nitrobenzoxazole isdissolved in 200 milliliters of n-propanol. A 10% palladium-on-carboncatalyst (2.0 grams) is added, and the mixture stirred under nitrogen.The mixture is heated to 70° C., and hydrogen gas is bubbled into themixture until substantially all the nitro groups have been reduced toprimary amine groups, as indicated by liquid chromatography. Thecatalyst is then filtered off and the remaining solution added to water.The solvent and water are then evaporated off to yield2-(m-aminophenyl)-5-aminobenzoxazole.

What is claimed is:
 1. A process for preparing a 2-(aryl)-benz(ox, thi,imid)azole, comprising:(a) contacting an aromatic aldehyde withhydroxylamine under conditions such that an aromatic aldehyde oxime isformed; (b) contacting said aromatic aldehyde oxime under aqueousconditions with hypochlorous acid formed in situ from a mixture of HCland a peroxysulfate salt or a mixture of sodium hypochlorite and aprotic acid such that an aromatic hydroxamoyl halide is formed; and (c)contacting the aromatic hydroxamoyl halide with an aromatic aminecompound which has a primary amine group ortho to a hydroxyl group, athiol group or another primary amine group to form a 2-(aryl)-benz(ox,thi, imid)azole.
 2. The process of claim 1 wherein neither the aromaticaldehyde nor the aromatic amine compound contains a nitro group, and theprocess further comprises the steps of contacting the 2-(aryl)-benz(ox,thi, imid)azole with a nitrating agent under conditions sufficient toadd a nitro group to each of the aromatic ring structures, and thenreducing the nitro groups to primary amine groups.
 3. The process ofclaim 2 wherein the aromatic aldehyde has a --CHO group bonded to apyridinyl, phenyl, anthracyl or naphthyl group.
 4. The process of claim3 wherein the aromatic amine compound is o-aminophenol.
 5. The processof claim 1 wherein the aromatic aldehyde is nitro-substituted on anaromatic nucleus.
 6. The process of claim 5 wherein the aromatic aminecompound is not nitro-substituted and a 2-(nitroaryl)-benz (ox, thi,imid)azole is formed, and wherein the process further comprises thesteps of contacting the 2-(nitroaryl)-benz(ox, thi, imid)azole with anitrating agent under conditions sufficient to add a nitro group to thearomatic ring structure fused to the (ox, thi, imid)azole ring, and thenreducing the nitro groups to primary amine groups.
 7. The process ofclaim 6 wherein the aromatic aldehyde has a --CHO group bonded to anitrophenyl, nitroanthracyl or nitronaphthyl group.
 8. The process ofclaim 7 wherein the aromatic amine compound is o-aminophenol.
 9. Theprocess of claim 6 wherein the aromatic amine compound isnitro-substituted on an aromatic nucleus and a2-(nitroaryl)-nitrobenz(ox, (thi, imid)azole is formed, and wherein theprocess further comprises reducing the nitro groups to primary aminegroups.
 10. The process of claim 9 wherein the aromatic aldehyde has a--CHO group bonded to a nitrophenyl, nitroanthracyl or nitronaphthylgroup.
 11. The process of claim 10 wherein the aromatic amine compoundis 2-amino-4-nitrophenol.